Competitor analogs for defined T cell antigens: peptides incorporating a putative binding motif and polyproline or polyglycine spacers.
We describe a new approach for modeling antigenic peptides recognized by T cells. Peptide A24 170-182 can compete with other antigenic peptides that are recognized by H-2kd-restricted cytolytic T cells, presumably by binding to the Kd molecule. By comparing substituted A24 peptides as competitors in a functional competition assay, the A24 residues Tyr-171, Thr-178, and Leu-179 were identified as possible contact residues for Kd. A highly active competitor peptide analog was synthesized in which Tyr was separated from the Thr-Leu pair by a pentaproline spacer. The choice of proline allowed the prediction of a probable conformation for the analog when bound to the Kd molecule. The simplest conformation of the A24 peptide that allows the same spacing and orientation of the motif as in the analog would be a nearly extended polypeptide chain incorporating a single 3(10) helical turn or similar structural kink.
Maryanski
J L
JL
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Verdini
A S
AS
Weber
P C
PC
Salemme
F R
FR
Corradin
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005998:Glycine; D006680:HLA Antigens / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D011392:Proline; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006680:HLA Antigens; D009842:Oligopeptides; D011392:Proline; D005998:Glycine